Maternal Smoking during Early Pregnancy,GSTP1 and EPHX1 Variants,and Risk of Isolated Orofacial Clefts

Abstract

Objective:

To examine the interactions between four fetal xenobiotic metabolizing gene polymorphisms, maternal cigarette smoking, and risk for oral cleft defects.

Design and Participants:

California population–based case-control study of 431 infants born with isolated orofacial clefts and 299 nonmalformed controls.

Main Outcome Measures:

Infants were genotyped for functional polymorphisms of the detoxification enzymes microsomal epoxide hydrolase-1 (EPHX1 T→C [Tyr113His], and A→G [His139Arg]), and glutathione-S transferase Pi-1 (GSTP1 A→G [Ile105Val] and C→T [Ala114Val]), and risks for cleft outcomes were measured for gene only and gene-maternal smoking effects.

Results:

Although smoking was associated with an increased risk for isolated cleft lip ± palate, we found no independent associations of genotypes of EPHX1-codon 113 or GSTP1-codon 105 polymorphisms for either isolated cleft lip ± palate or isolated cleft palate. The heterozygote genotype for the EPHX1-codon 139 polymorphism was associated with an increased risk of isolated cleft palate (odds ratio = 1.6 [95% confidence interval, 1.0 to 2.6]). Infant EPHX1 and GTSP1 polymorphic variants did not appreciably alter the risks for clefts associated with maternal smoking, nor were any EPHX1 combined genotype-specific risks found. Infant genotypes of the GSTP1-codon 105 polymorphism, combined with glutathione-S-transferase-μ-1 null genotypes, did not appreciably alter the risk of orofacial clefts.

Conclusions:

Our results suggest that genetic variation of the detoxification enzymes EPHX1 and GSTP1 did not increase the risks of orofacial clefting, nor do they influence the risks associated with maternal smoking.

Keywords

cleft lip cleft palate EPHX1 GSTM1 GSTP1 smoking

Get full access to this article

View all access options for this article.

References

Ahmad

Wilson

D.E.

Fritz

R.R.

Singh

S.V.

Medh

R.D.

Nagle

G.T.

Awasthi

Y.C.

Kurosky

Primary and secondary structural analyses of glutathione S-transferase pi from human placenta.

Arch Biochem Biophys. 1990; 278: 398–408.

Ali-Osman

Akande

Antoun

Mao

J.X.

Buolamwini

Molecular cloning, characterization, and expression in Escherichia coli of full-length cDNAs of three human glutathione S-transferase pi gene variants. Evidence for differential catalytic activity of the encoded proteins.

J Biol Chem. 1997; 272: 10004–10012.

Armstrong

R.N.

Enzyme-catalyzed detoxication reactions: mechanisms and stereochemistry.

CRC Crit Rev Biochem. 1987; 22: 39–88.

Arnould

J.P.

Verhoest

Bach

Libert

J.P.

Belegaud

Detection of benzo[a]pyrene-DNA adducts in human placenta and umbilical cord blood.

Hum Exp Toxicol. 1997; 16: 716–721.

Beaty

T.H.

Wang

Hetmanski

J.B.

Fan

Y.T.

Zeiger

J.S.

Liang

K.Y.

Chiu

Y.F.

Vanderkolk

C.A.

Seifert

K.C.

Wulfsberg

E.A.

Raymond

Panny

S.R.

McIntosh

A case-control study of nonsyndromic oral clefts in Maryland.

Ann Epidemiol. 2001; 11: 434–442.

Brunnemann

K.D.

Hoffmann

Analytical studies on tobacco-specific N-nitro-samines in tobacco and tobacco smoke.

Crit Rev Toxicol. 1991; 21: 235–240.

Fretland

A.J.

Omiecinski

C.J.

Epoxide hydrolases: biochemistry and molecular biology.

Chem Biol Interact. 2000; 129: 41–59.

Hansen

Sorensen

L.D.

Asmussen

Autrup

Transplacental exposure to tobacco smoke in human-adduct formation in placenta and umbilical cord blood vessels.

Teratog Carcinog Mutagen. 1992; 12: 51–60.

Hartsfield

J.K.

Jr Hickman

T.A.

Everett

E.T.

Shaw

G.M.

Lammer

E.J.

Finnell

R.H.

Analysis of the EPHX1 113 polymorphism and GSTM1 homozygous null polymorphism and oral clefting associated with maternal smoking.

Am J Med Genet. 2001; 102: 21–24.

10.

Hassett

Aicher

Sidhu

J.S.

Omiecinski

C.J.

Human microsomal epoxide hydrolase: genetic polymorphism and functional expression in vitro of amino acid variants.

Hum Mol Genet. 1994; 3: 421–428.

11.

Hassett

Lin

Carty

C.L.

Laurenzana

E.M.

Omiecinski

C.J.

Human hepatic microsomal epoxide hydrolase: comparative analysis of polymorphic expression.

Arch Biochem Biophys. 1997; 337: 275–283.

12.

Hayes

J.D.

Pulford

D.J.

The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance.

Crit Rev Biochem Mol Biol. 1995; 30: 445–600.

13.

Hosagrahara

V.P.

Rettie

A.E.

Hassett

Omiecinski

C.J.

Functional analysis of human microsomal epoxide hydrolase genetic variants.

Chem Biol Interact. 2004; 150: 149–159.

14.

Herzog

Zimniak

Singh

S.V.

Differential protection against benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide-induced DNA damage in HepG2 cells stably transfected with allelic variants of pi class human glutathione S-transferase.

Cancer Res. 1999; 59: 2358–2362.

15.

O'Donnell

Srivastava

S.K.

Xia

Zimniak

Nanduri

Bleicher

R.J.

Awasthi

Y.C.

Singh

S.V.

Active site architecture of polymorphic forms of human glutathione S-transferase P1-1 accounts for their enantioselectivity and disparate activity in the glutathione conjugation of 7beta,8alpha-dihydroxy-9alpha,10alpha-ox y-7,8,9,10-tetrahydrobenzo[a]pyrene.

Biochem Biophys Res Commun. 1997; 235: 424–428.

16.

Iovannisci

D.M.

Highly efficient recovery of DNA from dried blood using the MasterPure™ Complete DNA and RNA Purification Kit.

Epicentre Forum. 2000; 7: 6–8.

17.

Kelada

S.N.

Stapleton

P.L.

Farin

F.M.

Bammler

T.K.

Eaton

D.L.

Smith-Weller

Franklin

G.M.

Swanson

P.D.

Longstreth

W.T.

Checkoway

Glutathione S-transferase M1, T1, and P1 polymorphisms and Parkinson's disease.

Neurosci Lett. 2003; 337: 5–8.

18.

Lammer

E.J.

Shaw

G.M.

Iovannisci

D.M.

Finnell

R.H.

Maternal smoking during pregnancy, genetic variation of glutathione-S-transferases, and risk for orofacial clefts.

Epidemiology. 2005; 16: 698–701.

19.

Lieff

Olshan

A.F.

Werler

Strauss

R.P.

Smith

Mitchell

Maternal cigarette smoking during pregnancy and risk of oral clefts in newborns.

Am J Epidemiol. 1999; 150: 683–694.

20.

Morisseau

Hammock

B.D.

Epoxide hydrolases: mechanisms, inhibitor designs, and biological roles.

Annu Rev Pharmacol Toxicol. 2005; 45: 311–333.

21.

Oesch

Mammalian epoxide hydrases: inducible enzymes catalysing the inactivation of carcinogenic and cytotoxic metabolites derived from aromatic and olefinic compounds.

Xenobiotica. 1973; 3: 305–340.

22.

Oesch

Microsomal epoxide hydrolase. In: Jakoby

W.B.

, ed. Enzymatic Basis of Detoxication. Vol. 2. New York: Academic Press; 1980: 278.

23.

Omiecinski

C.J.

Hassett

Hosagrahara

Epoxide hydrolase—polymorphism and role in toxicology.

Toxicol Lett. 2000; 112–113: 365–370.

24.

Park

J.Y.

Schantz

S.P.

Stern

J.C.

Kaur

Lazarus

Association between glutathione S-transferase pi genetic polymorphisms and oral cancer risk.

Pharmacogenetics. 1999; 9: 497–504.

25.

Patrick

D.L.

Cheadle

Thompson

D.C.

Diehr

Koepsell

Kinne

The validity of self-reported smoking: a review and meta-analysis.

Am J Public Health. 1994; 84: 1086–1093.

26.

Raijmakers

M.T.

Steegers

E.A.

Peters

W.H.

Glutathione S-transferases and thiol concentrations in embryonic and early fetal tissues.

Hum Reprod. 2001; 16: 2445–2450.

27.

Robertson

I.G.

Guthenberg

Mannervik

Jernstrom

Differences in stereoselectivity and catalytic efficiency of three human glutathione transferases in the conjugation of glutathione with 7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene.

Cancer Res. 1986; 46: 2220–2224.

28.

Schottenfeld

Fraumeni

J.F.

Cancer Epidemiology and Prevention. New York: Oxford University Press; 1996.

29.

Shaw

G.M.

Wasserman

C.R.

Lammer

E.J.

O'Malley

C.D.

Murray

J.C.

Basart

A.M.

Tolarova

M.M.

Orofacial clefts, parental cigarette smoking, and transforming growth factor—alpha gene variants.

Am J Hum Genet. 1996; 58: 551–561.

30.

Sundberg

Johansson

A.S.

Stenberg

Widersten

Seidel

Mannervik

Jernstrom

Differences in the catalytic efficiencies of allelic variants of glutathione transferase P1-1 towards carcinogenic diol epoxides of polycyclic aromatic hydrocarbons.

Carcinogenesis. 1998; 19: 433–436.

31.

van Rooij

I.A.

Wegerif

M.J.

Roelofs

H.M.

Peters

W.H.

Kuijpers-Jagtman

A.M.

Zielhuis

G.A.

Merkus

H.M.

Steegers-Theunissen

R.P.

Smoking, genetic polymorphisms in biotransformation enzymes, and nonsyndromic oral clefting: a gene-environment interaction.

Epidemiology. 2001; 12: 502–507.

32.

Watson

M.A.

Stewart

R.K.

Smith

G.B.

Massey

T.E.

Bell

D.A.

Human glutathione S-transferase P1 polymorphisms: relationship to lung tissue enzyme activity and population frequency distribution.

Carcinogenesis. 1998; 19: 275–280.

33.

Wormhoudt

L.W.

Commandeur

J.N.

Vermeulen

N.P.

Genetic polymorphisms of human N-acetyltransferase, cytochrome P450, glutathione-S-transferase, and epoxide hydrolase enzymes: relevance to xenobiotic metabolism and toxicity.

Crit Rev Toxicol. 1999; 29: 59–124.

34.

Wyszynski

D.F.

Use of U.S. birth certificate data to estimate the risk of maternal cigarette smoking for oral clefting.

Cleft Palate Craniofac J. 2002; 39: 188–192.

35.

Zheng

Buffler

P.A.

Smith

M.T.

Wiencke

J.K.

Whole genome amplification increases the efficiency and validity of buccal cell genotyping in pediatric populations.

Cancer Epidemiol Biomarkers Prev. 2001; 10: 697–700.